ClinVar Miner

Submissions for variant NM_007294.4(BRCA1):c.3199A>T (p.Asn1067Tyr)

dbSNP: rs1597865137
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000817971 SCV000958559 uncertain significance Hereditary breast ovarian cancer syndrome 2022-07-21 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 1067 of the BRCA1 protein (p.Asn1067Tyr). This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BRCA1 protein function. ClinVar contains an entry for this variant (Variation ID: 660719). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions.
University of Washington Department of Laboratory Medicine, University of Washington RCV003158226 SCV003850920 likely benign Hereditary cancer-predisposing syndrome 2023-03-23 criteria provided, single submitter curation Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
Ambry Genetics RCV003158226 SCV004004326 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-24 criteria provided, single submitter clinical testing The p.N1067Y variant (also known as c.3199A>T), located in coding exon 9 of the BRCA1 gene, results from an A to T substitution at nucleotide position 3199. The asparagine at codon 1067 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV003158226 SCV004360240 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-22 criteria provided, single submitter clinical testing This missense variant replaces asparagine with tyrosine at codon 1067 of the BRCA1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BRCA1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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